Previous reports have suggested that bone morphogenetic protein (BMP) gene therapy could be applied for in vivo bone regeneration. However, these studies were conducted either using immunodeficient animals because of immunogenicity of adenovirus vectors, or using ex vivo gene transfer technique, which is much more difficult to handle. Adenoassociated virus (AAV) is a replication-defective virus without any association with immunogenicity and human disease. This study was conducted to investigate whether orthotopic new bone formation could be induced by in vivo gene therapy using AAV-based BMP2 vectors. To test the feasibility of this approach, we constructed an AAV vector carrying human BMP2 gene. Mouse myoblast cells (C2C12) transduced with this vector could produce and secrete biologically active BMP2 protein and induce osteogenic activity, which was confirmed by ELISA and alkaline phosphatase activity assay. For in vivo study, AAV-BMP2 vectors were directly injected into the hindlimb muscle of immunocompetent SpragueDawley rats. Significant new bone under X-ray films could be detected as early as 3 weeks postinjection. The ossification tissue was further examined by histological and immunohistochemical analysis. This study is, to our knowledge, the first to establish the feasibility of AAV-based BMP2 gene therapy for endochondral ossification in immunocompetent animals.
When fabricating metallic mechanism joints by selective laser melting (SLM), the clearance of the joint and the fabrication direction are two important factors, which are studied in this paper. In order to reduce joint clearance and facilitate the removal of support material, two improved joint designs are proposed: one with a drum-shaped hub design, and one with a drum-shaped pin design. As well as joint clearance, part strength is also very important. Sample tensile test parts were fabricated by SLM and tested for yield strength and elongation: these mechanical properties were comparable to those of equivalent parts produced by casting. For experimental verification, a number of metallic joints are fabricated. Since non-assembled metallic mechanisms produced by SLM have strength that can stand large loads, they have the potential to be used directly as mechanical power transmission systems in some practical applications.
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